Charles Thompson lived his life for the most part in Saint Louis, Missouri, where he was born and raised. June 19th has also been cited as his birth date, but his birth record and 1917 draft card clearly show June 9. The 1900 enumeration showed him as an only child living with his mother, Laura Hubbard, his father Charles N. Thompson having evidently left. Charley was mostly self-taught, having received only a few formal lessons, and had virtually no notation skills. By the time he was 20, Thompson was well involved in the Saint Louis music scene, often touring wherever the work would take him. He was known for being a black key player, preferring to eschew the easier keys like C or F because they inhibited his ebullient style. His most famous work, Lily Rag, was deftly arranged for publication by fellow pianist and pastime rag composer Artie Matthews and issued by classic ragtime publisher John Stark. It has remained a delightful challenge to pianists since its publication.

During the early 1910s Thompson chose the life of an itinerant pianist and set out to play around the country. He was known to have played in Detroit, Michigan; Cleveland and Toledo, Ohio (he would live in the latter for a time in the early 1920s); Buffalo, New York, the very active Bowery at Coney Island, New York (where Jimmy Durante among others was performing regularly); and Washington, DC. Back in Saint Louis, one famous story about Thompson involves a massive ragtime piano competition/playoff in 1916 at Tom Turpin's Booker T. Washington Theater, in which the best of the best was to be decided. All of the famous Police Gazette contest players showed up, as did many of Saint Louis' finest, including the imposing host, Turpin himself. In total, 68 players entered this contest which lasted a full two weeks. Thompson came out on top of them all, and was declared Missouri State Champion, although it might as well have been World Champion at that point. His 1917 World War I draft card shows Charley as married and supporting his mother, and as a musician employed by Mr. A Hunter across the Mississippi river in Brooklyn, Illinois.

In 1919, Charley met with developing stride pianist James P. Johnson (some sources erroneously cite 1912 when Johnson would have been only 18, but they may have met initially around 1916), who was still working out the Harlem piano sound. Johnson's influence was heard almost immediately in Thompson's playing and composing. He was also known to put out some memorable blues tunes. Thompson continued playing in Saint Louis until the district where the ragtime was played was shut down in the wake of Storyville being closed in New Orleans, all in an effort to clean out prostitution and drugs from the inner cities. In 1920, now divorced, he was shown working as a theater musician back in Toledo, Ohio, but eventually returned to Saint Louis.

In subsequent years, Thompson became a very accomplished chef, and at one time is reported to have plied his trade on the Pennsylvania Railroad cooking on the rails. The time period of this activity is a bit fuzzy, however, and may have been sporadic. In spite of these travels, Charlie was still based in Saint Louis, found there in the 1930 census living with his mother Laura and another lodger, and working as an orchestra musician. Charlie both married in the early 1930s and switched careers during the decade of the Great Depression, which had been somewhat brutal to the Midwest given the added grief of drought conditions. For the 1940 enumeration he was found again residing in Saint Louis with his mother Laura and new wife Nona, now working as a professional electrician, with Nona employed as a hotel maid. By the time of the 1950 census, it appeared that Charlie now ran his own tavern, and Nona was his primary barmaid. Further details on this outside of the census were difficult to locate.

With a renewed interest in ragtime and stride piano in the mid to late 1940s, Charlie was able to once again play on a regular basis in Saint Louis pretty much through the end of his life. He even made several recordings of his own compositions and other popular tunes in the late 1940s into the 1950s. Some of these short tracks were released on Herwin Records in the 1970s. Some later ones recorded at ragtime house parties held by pianist and historian Trebor Tichenor, are still available on a Euphonic CD titled The Neglected Professor.

There was one more fine moment in store for him. In 1962, Bob Darch, who had worked on presenting a number of Thompson appearances in the late 1950s, arranged for a Florida recording session for Charlie and two of his friends from the past, Joe Jordan and Eubie Blake. The resulting session, in glorious stereo, was edited down to the Golden Reunion in Ragtime on the Stereoddities label, as well as a radio show version, and was one of the most joyous occasions of his later life, which sadly ended two years later. Even at that, he met with the inequality that still existed in the South in the early 1960s, as it was found that hotels in Fort Lauderdale would not host the three black performers, forcing them to be driven up to the studio from Miami by Darch. There are currently plans in the works to release the entirety of the Steroddities sessions in 2017.